Liver fat content is linked to inflammatory changes in subcutaneous adipose tissue in type 2 diabetes patients

• Published in: Clinical endocrinology (Oxford) Vol. 79; no. 5; pp. 661 - 666
• Main Authors: Jansen, Henry J., Vervoort, Gerald M., van der Graaf, Marinette, Stienstra, Rinke, Tack, Cees J.
• Format: Journal Article
• Language: English
• Published: Oxford Blackwell Publishing Ltd 01-11-2013; Blackwell; Wiley Subscription Services, Inc
• Subjects: Adipose Tissue - metabolism; Biological and medical sciences; Cross-Sectional Studies; Diabetes; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - immunology; Diabetes Mellitus, Type 2 - metabolism; Diabetes. Impaired glucose tolerance; disease; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fats - metabolism; Female; Fundamental and applied biological sciences. Psychology; hepatic steatosis; Humans; hypoadiponectinemia; Inflammation - metabolism; Insulin - therapeutic use; insulin-resistance; Liver; Liver - metabolism; macrophage infiltration; Male; Medical sciences; mellitus; mice; Middle Aged; obese individuals; Obesity - metabolism; plasminogen-activator inhibitor-1; Proteins; risk; Subcutaneous Fat - immunology; Subcutaneous Fat - metabolism; Vertebrates: endocrinology; Endocrinopathy; Type 2 diabetes; Human; Adipose tissue; Digestive system; Liver; Metabolic diseases; Patient; Fat content; Inflammation; Change; Subcutaneous tissue; Endocrinology
• ISSN: 0300-0664; 1365-2265
• DOI: 10.1111/cen.12105

Summary
Background
Patients with type 2 diabetes mellitus (T2DM) are typically overweight and have an increased liver fat content (LFAT). High LFAT may be explained by an increased efflux of free fatty acids from the adipose tissue, which is partly instigated by inflammatory changes. This would imply an association between inflammatory features of the adipose tissue and liver fat content.
Objective
To analyse associations between inflammatory features of the adipose tissue and liver fat content.
Design
A cross‐sectional study.
Patients
Twenty‐seven obese patients with insulin‐treated T2DM were studied.
Measurements
LFAT content was measured by proton magnetic resonance spectroscopy. A subcutaneous (sc) fat biopsy was obtained to determine morphology and protein levels within adipose tissue. In addition to fat cell size, the percentage of macrophages and the presence of crown‐like structures (CLSs) within sc fat were assessed by CD68‐immunohistochemical staining.
Results
Mean LFAT percentage was 11·1 ± 1·7% (range: 0·75–32·9%); 63% of the patients were diagnosed with an elevated LFAT (upper range of normal ≤5·5%). Whereas adipocyte size did not correlate with LFAT, 3 of 4 subjects with CLSs in sc fat had elevated LFAT and the percentage of macrophages present in sc adipose tissue was positively associated with LFAT. Protein concentrations of adiponectin within adipose tissue negatively correlated with LFAT. Adipose tissue protein levels of the key inflammatory adipokine plasminogen activator inhibitor‐1 (PAI‐1) were positively associated with LFAT.
Conclusions
Several pro‐inflammatory changes in sc adipose tissue associate with increased LFAT content in obese insulin‐treated patients with T2DM. These findings suggest that inflammatory changes at the level of the adipose tissue may drive liver fat accumulation.